Cyclohexadepsipeptides (CHDPs) with improved anthelmintical efficacy against the gastrointestinal nematode (Haemonchus contortus) in sheep

被引：4

作者：

Jeschke P. ^{[1
]}

Harder A. ^{[2
]}

Schindler M. ^{[1
]}

Etzel W. ^{[1
]}

机构：

[1] Bayer CropScience AG, Research and Development Chemistry Insecticides, 40789 Monheim am Rhein

[2] Bayer HealthCare AG, Animal Health Division, Research and Development Parasiticides, Leverkusen

来源：

Parasitology Research | 2005年 / 97卷 / Suppl 1期

关键词：

Gastrointestinal Nematode; Anthelmintic Activity; Anthelmintic Resistance; Depsipeptide; Emodepside;

D O I：

10.1007/s00436-005-1440-5

中图分类号：

学科分类号：

摘要：

Besides 24-membered cyclooctadepsipeptides (CODPs) with the most prominent member of this class emodepside, the structurally related 18-membered cyclohexadepsipeptides (CHDPs) were of interest with regard to their efficacy against the nematode H. contortus in sheep. The CHDPs prepared by a simple total synthesis represent enniatin derivatives with strong in vivo activity against H. contortus in sheep. The correlation between the nature of the CHDP major conformers and their anthelmintic activities was studied in detail. All CHDPs with strong in vivo activity exists in deuterochloroform solution as conformers with restricted flexibility which was found by 2D-NMR spectroscopic analysis. This reduced flexibility of the major conformer can be exemplified by CHDPs containing e.g.: (i) an unsymmetrically folded conformation with no cis-amide bound, (ii) an internal hydrogen bond or (iii) one cis-amide bond, respectively. The strong in vivo anthelmintic activity against H. contortus in sheep indicates that the stereochemistry in 2-position of CHDPs is less important for their high binding affinity. It may be assumed that the identified inflexible region of the major conformers might mimic the active conformation of these CHDPs, which could be helpful for rational design of anthelmintics with less complicated structures.

引用

页码：S17 / S21

页数：4

共 15 条

[11] Pleiss U., Turberg A., Harder A., Londershausen M., Jeschke P., Boheim G., Synthesis of radiolabeled enniatin cyclodepsipeptide [ <sup>3</sup>H-methyl] JES1798, J. Labelled Comp. Radiopharm., 38, pp. 651-659, (1996)
[12] Von Samson-Himmelstjerna G., Harder A., Schnieder T., Kalbe J., Geerts S., Coles G.C., Gryseels B., Anthelmintic resistance in human helminths: Learning from the problems with worm control in livestock, Parasitol. Today, 13, (1997)
[13] Sangster N., Batterham P., Chapman H.D., Duraisingh M., Jambre L.L., Shirley M., Upcroft J., Upcroft P., Resistance to antiparasitic drugs: The role of molecular diagnosis, Int. J. Parasitol., 32, pp. 637-653, (2002)
[14] Scherkenbeck J., Jeschke P., Harder A., PF1022A and Related Cyclodepsipeptides - A novel class of anthelmintics, Current Topics Med. Chem., 2, pp. 759-777, (2002)
[15] Schnyder M., Torgerson P.R., Schonmann M., Kohler L., Hertzberg H., Multiple anthelmintic resistance in Haemonchus contortus isolated from South African Boer goats in Switzerland, Vet. Parasitol., 128, pp. 285-290, (2005)

← 1 2 →